Abstract | BACKGROUND: This study tested the hypothesis that response of adrenal cortical carcinoma (ACC) to pro-apoptosis drugs depends on expression of anti-apoptosis genes. MATERIALS AND METHODS: Expression of Bcl-2 and Bcl-XL proteins was determined in two human adrenal cancer cell lines, NCI-H-295 and RL-251. Two pro-apoptosis drugs, gossypol (G) and docetaxel (D) were tested in vitro and in vivo in a human ACC/SCID mouse chimera. RESULTS: Bcl-XL was strongly expressed in RL-251 but not in H-295 and neither expressed the Bcl-2 protein. G and D induced greater dose-dependent inhibition of cell proliferation in RL-251 than in H-295 cells and completely suppressed growth of tumors with high expression of Bcl-XL (p<0.05) while there was no growth suppression in tumors without Bcl-XL expression. CONCLUSION: This study provided proof of concept that expression of Bcl-XL determines response to pro-apoptosis drugs. Profiling adrenal tumors for expression of anti-apoptosis genes may provide clues to their potential response to drugs that induce apoptosis.
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Authors | David E Schteingart, Ricardo Benitez, Carol Bradford, Ajita Narayan, Shaomeng Wang |
Journal | Anticancer research
(Anticancer Res)
Vol. 30
Issue 12
Pg. 4805-9
(Dec 2010)
ISSN: 1791-7530 [Electronic] Greece |
PMID | 21187456
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- BCL2L1 protein, human
- Proto-Oncogene Proteins c-bcl-2
- Taxoids
- bcl-X Protein
- Docetaxel
- Gossypol
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Topics |
- Adrenal Cortex Neoplasms
(drug therapy, genetics, metabolism, pathology)
- Animals
- Apoptosis
(drug effects, genetics)
- Cell Line, Tumor
- Docetaxel
- Genes, bcl-2
- Gossypol
(pharmacology)
- Humans
- Mice
- Mice, SCID
- Proto-Oncogene Proteins c-bcl-2
(biosynthesis, genetics)
- Taxoids
(pharmacology)
- bcl-X Protein
(biosynthesis, genetics)
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